The studies described in this proposal continue our work on the immunogenicity of synthetic polypeptide antigens and expanded into an integrated chemical, genetic and cellular approach to our long-term objectives of explaining in chemical terms how an antigen acts to elicit an antibody response and what the molecular basis of the genetically controlled differences in the response are. Studies on the genetic control of the antibody response have led to free development of a polygenic model for the control of antibody response. There is a sex influence on the immune response: the amount of antibody formed by females is larger and more heterogeneous than that formed by males. We are presently trying to determine whether this sex influence is genetic and/or hormonal. The maternal-fetal interaction can markedly affect the ability of the fetus to respond to an antigenic stimulus: immunization of the mother enhances the ability of the offspring to form antibody. This effect is being studied to determine the mechanism by which it occurs.